Laboratory Studies

The results of all blood studies, including cholesterol triglyceride level, phospholipid levels, free fatty acid levels, glucose determinations, and lipoprotein serum fraction, are within the reference range in most verruciform xanthoma patients in whom these studies were carried out, with the following exceptions: one patient with diabetes mellitus, one patient with increased serum cholesterol levels, and one patient with a lipid storage disease.

Histologic Findings

Similar to their range of clinical presentations, verruciform xanthomas may appear verrucous, papillary, or cauliflowerlike, or they may show a lichenoid pattern histologically. A mixture of the above patterns may also be observed. A variable degree of parakeratosis is observed that is usually more marked in verrucous and papillary lesions, with parakeratosis present in the crypts between papillae. No epithelial atypia is present. The lesion is exophytic, with the rete ridges in the lesion not extending into the underlying dermis. The connective-tissue papillae are of variable length and thickness; they often extend close to the surface. The papillae may be extremely long and thin. Rarely, the entire process may occur in a cystlike structure.

The most striking and characteristic histologic feature of the verruciform xanthoma is the presence of large foam cells in the connective-tissue papillae.^[91]These cells characteristically fill the entire papilla but only rarely extend beyond the base of the papilla. Most or all of the papillae are involved with these cells, which occasionally may also be seen in the epithelium (ie, epidermis, mucosa).

Ultrastructurally, most studies have concluded that the foam cells in verruciform xanthoma are fat-laden macrophages, although other cell types, including Langerhans cells and even fibroblasts, have been proposed. Immunohistochemical analysis revealed these cells to be positive for LCA and CD68 and negative for S100, a marker pattern also characteristic of macrophages. A few S100-negative dendritic or granular cells have been reported in these lesions as well and may represent Langerhans cells. The contents of the cells stain with lipid stains, and the vacuoles that contain this material are decorated by anti–human lysosome antibody. They are also periodic acid-Schiff (PAS) positive and diastase resistant, indicating that the PAS-positive material is not glycogen.

At electron microscopy, this material also demonstrates the appearance of lipid. Chemical studies by gas chromatography of extracted material show a preponderance of cholesterol esters. In addition to the lipid material, Zagarelli et al also noted the presence of what they interpreted as degenerating epithelial cells in the foam cells.^{[11, 92]}Cobb et al described myelin figures and reduplication of the overlying basal lamina and fibroblasts in addition to macrophagelike cells, which contained lipid inclusions.^[93]

A slight inflammatory infiltrate may be present beneath the verruciform xanthoma lesion. Occasional verruciform xanthomas have been associated with a massive or lichenoid infiltrate. No granulomatous change has been described other than the presence of the foamy macrophages. Microorganisms are not characteristically present. Although bacteria and fungal hyphae are occasionally described, they appear to play no role in the etiopathogenesis. The results of extensive probing for viruses have been negative.

Dermoscopic Findings

Dermoscopy can be useful for verruciform xanthoma, and it reveals surface papilla containing linear or hairpin vessels, surrounded by a marginal whitish rim. These structures are thought to correspond to dilated vessels in dermal papillae and papillated acanthotic epidermis. Under compression, the vessels disappear, and yellow dots and debris reflecting lipid-laden foam cells become visable.^[94]

Treatment & Management

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Xanthelasma. Courtesy of Duke University Medical Center.

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Author

W Clark Lambert, MD, PhD Clinical Professor of Pathology, Clinical Professor of Medicine (Professor of Dermatology), Rutgers New Jersey Medical School; Professor of Pathology, Rutgers Graduate School of Biomedical Sciences

W Clark Lambert, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, American Dermatological Association, American Federation for Clinical Research, American Society of Dermatopathology, College of American Pathologists, Dermatological Society of New Jersey, Institute of Electrical and Electronics Engineers, International Academy of Pathology, International Federation of Pigment Cell Societies, International Society of Dermatopathology, Medical Society of New Jersey, Sigma Xi, The Scientific Research Honor Society, Society for Investigative Dermatology, Xeroderma Pigmentosum Society

Disclosure: Nothing to disclose.

Coauthor(s)

Hong Li, MD Pathologist and Dermatopathologist

Hong Li, MD is a member of the following medical societies: American Society for Clinical Pathology, College of American Pathologists

Disclosure: Nothing to disclose.

Fernanda Salgado Rutgers New Jersey Medical School

Fernanda Salgado is a member of the following medical societies: American Medical Association, Latino Medical Student Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael J Wells, MD, FAAD Dermatologic/Mohs Surgeon, The Surgery Center at Plano Dermatology

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Jeffrey P Callen, MD Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine

Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, American College of Rheumatology

Disclosure: Received income in an amount equal to or greater than $250 from: Biogen US (Adjudicator for study entry cutaneous lupus erythematosus); Priovant (Adjudicator for entry into a dermatomyositis study); IQVIA (Serono - adjudicator for a study of cutaneous LE) <br/>Received honoraria from UpToDate for author/editor; Received royalty from Elsevier for book author/editor; Received dividends from trust accounts, but I do not control these accounts, and have directed our managers to divest pharmaceutical stocks as is fiscally prudent from Stock holdings in various trust accounts include some pharmaceutical companies and device makers for these trust accounts for: Stocks held in various trust accounts: Allergen; Amgen; Pfizer; 3M; Johnson and Johnson; Merck; Abbott Laboratories; AbbVie; Procter and Gamble;; Celgene; Gilead; CVS; Walgreens; Bristol-Myers Squibb.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD<br/>Served as a speaker for various universities, dermatology societies, and dermatology departments.

Additional Contributors

Peter C Lambert, MS St George's University School of Medicine, Grenada

Disclosure: Nothing to disclose.

Verruciform Xanthoma Workup

Laboratory Studies

Histologic Findings

Dermoscopic Findings

References

Tables

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